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Relative Contributions of α 4 and α L Integrins to IL‐4‐Induced Leukocyte Rolling and Adhesion
Author(s) -
EPPIHIMER MICHAEL J.,
SUSHKOVA NATALIA,
LAVIGNE MARK C.
Publication year - 2004
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680490517677
Subject(s) - integrin , intravital microscopy , adhesion , monoclonal antibody , cd8 , chemistry , cell adhesion , microbiology and biotechnology , immunology , cell adhesion molecule , microcirculation , antibody , medicine , biology , antigen , cell , biochemistry , organic chemistry
Objective: To delineate the relative contributions of α 4 and α L to mediate interleukin‐4 (IL‐4) induced leukocyte rolling, and the subsets of leukocytes that use these pathways to adhere. Methods: Intravital microscopy was used to examine leukocytes in venules of cremaster muscles of mice receiving intrascrotal injections of IL‐4. α 4 and α L monoclonal antibodies (mAbs) were administrated either prior to (prophylactic) or 24 h following (therapeutic) treatment with IL‐4. In addition, fluorescent microspheres coated with mAbs directed against CD4, CD8, or Gr‐1 were injected into mice and the number of subset‐specific adherent leukocytes was measured. Results: Prophylactic inhibition of α 4 and α L integrins prevented IL‐4‐induced leukocyte rolling flux ( p < .05) and increased leukocyte rolling velocity twofold ( p < .05), respectively, while blocking either integrin eliminated IL‐4‐induced leukocyte adhesion ( p < .05). In contrast, therapeutic administration of both anti‐α 4 and anti‐α L mAbs was necessary to completely inhibit IL‐4‐induced leukocyte adhesion ( p < .05). Furthermore, CD8 + and Gr‐1 + leukocytes utilized α 4 and α L to adhere to postcapillary venules, whereas CD4 + leukocytes primarily utilized α 4 . Conclusions: Following tissue activation with IL‐4, α 4 and α L initiate the attachment and deceleration, respectively, of leukocytes during rolling, and are responsible for mediating the adhesion CD4 + , CD8 + , Gr‐1 + leukocytes.